What are the potential side effects and management strategies for a patient with Myasthenia Gravis (MG) being considered for Rituximab (rituximab) therapy?

Rituximab Side Effects in Myasthenia Gravis

Rituximab can cause serious infusion reactions, severe infections (including fatal opportunistic infections), cardiac events, tumor lysis syndrome, and progressive multifocal leukoencephalopathy, but appears well-tolerated in MG patients when appropriately monitored, with particular efficacy in MuSK-antibody positive disease. 1, 2

Critical Life-Threatening Side Effects

Infusion-Related Reactions

• Severe or fatal infusion reactions can occur during or within 24 hours of rituximab administration, manifesting as hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock 1
• Premedication with acetaminophen and antihistamine is mandatory before each infusion 1
• Immediate discontinuation is required for severe reactions, with aggressive supportive care 1

Severe Infections

• Serious bacterial, fungal, and viral infections can occur during and after treatment, leading to death 1
• Hepatitis B virus reactivation can result in fulminant hepatitis, hepatic failure, and death—all patients must be screened for HBV before initiating therapy 1
• Progressive multifocal leukoencephalopathy (PML), a fatal brain infection caused by JC virus, has been reported with rituximab 1
• Patients develop prolonged hypogammaglobulinemia (low antibody levels lasting >11 months), increasing infection susceptibility 1

Cardiac Complications

• Rituximab may cause chest pain, irregular heartbeats, heart attack, and fatal cardiac events 1
• Cardiac monitoring during and after infusion is essential in patients with pre-existing heart disease or cardiac symptoms 1

Hematologic and Metabolic Toxicities

Tumor Lysis Syndrome

• TLS occurs within 12-24 hours after infusion, causing kidney failure requiring dialysis, abnormal heart rhythm, and potentially death 1
• Aggressive IV hydration and anti-hyperuricemic agents are required, with close monitoring of renal function and electrolytes 1
• Symptoms include nausea, vomiting, diarrhea, and lack of energy 1

Cytopenias

• Prolonged and severe cytopenias including neutropenia and thrombocytopenia can occur 1
• Regular complete blood count monitoring is necessary throughout treatment 1

Organ-Specific Toxicities

Renal Toxicity

• Severe kidney problems leading to death can occur, particularly in NHL patients 1
• Discontinue rituximab immediately if serum creatinine rises or oliguria develops 1
• Serial renal function monitoring is mandatory 1

Gastrointestinal Complications

• Bowel obstruction and perforation, sometimes fatal, can occur when rituximab is combined with chemotherapy 1
• Evaluate immediately for severe abdominal pain or repeated vomiting 1

MG-Specific Considerations

Clinical Efficacy and Safety Profile in MG

• In MG patients, rituximab appears well-tolerated with encouraging safety data, though serious adverse events can occur 2, 3
• The evidence suggests little difference in serious adverse events compared to placebo in MG trials, though certainty is very low (RR 0.81,95% CI 0.47 to 1.41) 3
• One study of 14 MG patients reported no serious adverse events with low-dose rituximab (1g total dose) 4

MuSK-Positive Disease

• Rituximab demonstrates particular effectiveness in MuSK-antibody positive MG with good tolerability 5, 2
• A patient with MuSK-positive MG showed no severe infectious complications after 10 years of rituximab treatment 5

Monitoring Strategy for MG Patients

• Serial peripheral blood B lymphocyte monitoring by flow cytometry guides retreatment timing 4
• B cell recovery occurs 9-30 months post-rituximab (median 12.3 months) and consistently correlates with symptom worsening 4
• Clinical assessments using Quantitative MG scores and MG-ADL scales track therapeutic response 3

Common Non-Life-Threatening Side Effects

• Infusion-related reactions (most common): fever, chills, rigors 1
• Infections including upper respiratory tract infections 1
• Body aches, tiredness, nausea 1
• Aching joints during or within hours of infusion 1

Critical Management Pitfalls

Vaccination Considerations

• Live virus vaccines are contraindicated before or during rituximab treatment 1
• Plan vaccinations well in advance of initiating therapy 1

Pregnancy and Contraception

• Rituximab causes fetal harm and B cell depletion in neonates 1
• Effective contraception is mandatory during treatment and for 12 months after the last dose 1

Drug Interactions in MG

• Avoid medications that worsen myasthenia: beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 6

Dosing Regimen Safety

• The standard 375 mg/m² weekly for 4 weeks regimen studied in clinical trials is well-established 5
• Low-dose protocols (1g total in two divided doses) show similar efficacy with potentially reduced toxicity in MG 4, 7
• Regular hematological monitoring is not required for rituximab, unlike conventional oral immunosuppressants, though surveillance for infections and B cell counts remains important 2, 4